Pursuant to our discovery (1971) of a photochemical method for the synthesis of fluoroimidazoles, we have found that fluoro derivatives of various bioimidazoles (histamine, histidine, etc.) possess a variety of useful properties as biological substrates and inhibitors. 2-Fluoro-L-histidine, for example, not only is incorporated into bacterial and animal protein in place of histidine, but also serves as an antibacterial, antiviral and antileukemic agent. These, and other, biological properties appear to be specific for the 2-fluoro isomer. In the course of efforts to determine how the various recognition sites differentiate between the 2- and 4-fluoro isomers, we have undertaken the syntheses of 2,4-difluoroimidazoles. These efforts have proved to be extremely laborious, but the desired products have not been obtained and biological studies have been initiated. 4-Fluoro-Im-TRH failed to bind to rat pituitary cells in vitro and failed to stimulate prolactin release. On the other hand, microinjection of this compound into the rat hypothalamus results in strong evaluations in heart rate and blood pressure. Thus, the long-sought separation of the pituitary and CNS activities of TRH have been achived by means of a fluoro analog. Additional analogs are being synthesized in the hope of achieving stability to hydrolytic breakdown without loss of selectivity. Fluoroimidazoles are obtainedby photochemical replacement of amino groups and aminoimidazoles are generally prepared by reduction of arylazoimidazoles. Thus, 4-fluoro-2-aminoimidazole-5-carboxamide was prepared and was converted into the 2,4-difluoro derivative. Surprisingly, the isomeric 2-fluoro-4-aminoimidazoles are far less stable and must be stored at very low temperatures. In parallel with the broad-spectrum antiviral activities shown by 4-fluoroimidazole-5-carboxamide, the new compounds will also be investigated for such activities.